Clinical Characteristics and Outcomes of Patients Hospitalized with COVID-19 at Case Hospital, Uganda

Data on clinical outcomes of patients hospitalized with coronavirus disease 2019 (COVID-19) in private health facilities in Uganda is scarce. We conducted a retrospective cohort study of patients hospitalized with COVID-19 at Case Hospital, Kampala, Uganda, between June 2020 and September 2021. Data of 160 participants (median age 45 years (interquartile range [IQR]: 37–57) and 63.5% male) was analyzed. Seventy-seven (48.1%) participants had non-severe, 18 (11.3%) severe, and 83 (51.9%) critical COVID-19 illness. In 62 participants with chest computed tomography findings, 54 (87%) had bilateral disease, with 22 (35%) having ground-glass opacities. The median duration of hospitalization was 5 days (IQR: 3–9 days). Overall, 18 (11.3%) participants died. Survival at 14 and 28 days was 89% and 72%, respectively. Factors strongly associated with all-cause mortality were as follows: age >50 years (odds ratio [OR]: 8.6, 95% confidence interval [CI]: 1.1–69.2, and p=0.042), having at least 1 comorbidity (OR: 3.2, 95% CI: 1.1–8.9, and p=0.029), hypertension (OR: 3.2, 95% CI: 1.2–8.6, and p=0.024), diabetes mellitus (OR: 2.9, 95% CI: 1.0–8.5, andp=0.056), and oxygen saturation <92% (OR: 5.1, 95% CI: 1.8–14.4, and p=0.002). In this private health facility, mortality was about 1 in 10 patients, and more people presented with critical illness in the second wave of the pandemic, and most deaths occurred after 2 weeks of hospitalization.


Introduction
e coronavirus disease 2019 (COVID- 19), which was first reported as a pneumonia of unknown etiology in Wuhan, Hubei Province, China, at the end of 2019, is an emerging viral illness caused by the novel beta coronavirus known as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) [1,2]. COVID-19 is an important global public health concern and is currently the leading cause of death from a single infectious agent, with an estimated 530 million cases resulting in over 6.3 million deaths in about 30 months [3].
COVID-19 is a multisystemic disease with varying clinical manifestations and severity depending on several host factors such as age, immune status, and the presence of co-morbidities [4,5]. However, recently, some variants of SARS CoV-2 have been shown to be more transmissible and pathogenic and are associated with more symptomatic disease, severe/critical illness, and breakthrough infections in patients who have received the COVID-19 vaccine [6]. Most patients with COVID-19 are asymptomatic [7]. In those who are symptomatic; cough, chest pain, loss of smell, and nasal congestion as well as other extrapulmonary symptoms such as fever, joint paints, and headaches are the most common symptoms [8,9]. However, about 5 to 15% of patients present with severe and/or critical disease characterized by acute respiratory distress syndrome and/or coagulopathy due to an exaggerated host immune response, also known as, the cytokine storm [10]. Previous studies have identified risk factors for severe/critical COVID-19 illness as the presence of comorbidities such as diabetes mellitus, hypertension, and obesity [11][12][13]. ese are the group of individuals with the highest risk of mortality and morbidity due to COVID-19 [14].
Uganda has experienced 3 waves of the COVID-19 pandemic and recently experienced the third wave, with a rapid increase in the number of cases in mid-December 2021 and confirmation of the omicron variant, which spread very rapidly, globally. In the first wave, the first case of COVID-19 was reported on the 20 th of March 2020, and in the middle of April 2021, a second surge in the number of COVID-19 cases was observed. As of 27 th May 2022, over 164,000 cases and 3,596 COVID-19-related deaths have been reported as the country battles the third wave of the pandemic, predominantly with the omicron variant [3]. e first 100 cases were predominantly asymptomatic or mild cases with 100% survival [15,16]. However, in the second wave, mortality was as high as 36% at the National COVID-19 Treatment Unit (CTU) [17].
Our understanding of the clinical presentation, radiological features, and outcomes of patients hospitalized with COVID-19 in Uganda is incompletely understood, with currently published studies based only on data from selected CTUs in public health facilities [16,17]. However, data regarding the clinical presentation, imaging findings, and outcomes of patients with COVID-19 in private facilities in Uganda is still lacking. Here, we report on the clinical characteristics, treatment, and outcomes of patients with COVID-19 hospitalized at a CTU of a major private facility in Uganda.

Study Design.
is was a descriptive, single-center, retrospective cohort study of patients hospitalized with COVID-19 at Case Hospital, Kampala, Uganda, between June 2020 and September 2021.

Study Setting.
Case Hospital (also known as Case Medical Centre), established in 1995, is an urban, private, upscale, tertiary hospital situated in the heart of Kampala, Uganda. Case Hospital offers specialized, multidisciplinary healthcare in an 80-bed facility with a fully equipped intensive care unit, laboratory facilities, and state-of-the-art imaging modalities. Case Hospital started receiving patients with COVID-19 in early May 2020. e hospital has been accredited by the Ministry of Health of Uganda as a CTU.

Study Population.
We included data of all patients hospitalized with a confirmed diagnosis of COVID-19 during the study period. COVID-19 was diagnosed by polymerase chain reaction and SARS-CoV-2 rapid antigen test, with or without a compatible chest imaging. We imaging. We excluded patients transferred out of the facility for whom outcome records could not be traced.

Data Collection.
ree trained research assistants collected data regarding demographics (age, sex, occupation, level of education, etc.), comorbidities, HIV status, clinical symptoms and duration, clinical findings, severity of the disease, radiological findings, laboratory findings, prescription information concerning drugs (dose and duration), interventions (oxygen and mechanical ventilation), duration of hospitalization, and outcomes at discharge (alive or dead).

Definition of COVID-19
Disease Severity. Disease severity was defined according to the World Health Organization (WHO) Severity definitions [18].

Critical COVID-19.
Defined by the criteria for acute respiratory distress syndrome (ARDS), sepsis, septic shock, or other conditions that would normally require the provision of life-sustaining therapies such as mechanical ventilation (invasive or noninvasive) or vasopressor therapy. . Defined by any of (1) oxygen saturation <90% on room air, (2) respiratory rate >30 breaths/min in adults, (3) signs of severe respiratory distress (accessory muscle use, inability to complete full sentences, and, in children, very severe chest wall indrawing, grunting, central cyanosis, or the presence of any other general danger signs).

Non-Severe COVID-19.
Defined as the absence of any criteria for severe or critical COVID-19.
2.6. Data Analysis. Anonymized data was analyzed using STATA version 16.0 (StataCorp LLC, College Station, Texas, USA). We summarized continuous variables using means with standard deviations or medians with interquartile range (IQR) and categorical variables using frequencies and percentages. Chi-square test was performed to compare categorical variables, and Mann-Whitney U and t-tests for nonparametric and parametric continuous variables, respectively. A multivariable logistic regression model was constructed for the analysis of treatment outcomes accounting for all important confounders. e results of the logistic regression models were presented as odds ratios (ORs) with 95% confidence intervals (95% CIs). Kaplan-Meier survival analysis was performed to determine 14-and 28-day in-hospital mortality and time-to-event. For all analyses, p < 0.05 was considered statistically significant.

Ethical Considerations.
e Mulago Hospital Research and Ethics Committee (MHREC) approved the study protocol and provided a waiver of informed consent of the study participants (approval reference: MHREC 2065). All ethical principles outlined in the Declaration of Helsinki were observed.
ere were surges in admissions between October-December 2020 and April-July 2021, coinciding with the first and second waves of COVID-19 in Uganda ( Figure 1).

Chest
Imaging. Chest CT and/or X-ray scans were done in 88 (55%) patients and 77 (87.5%) had abnormal findings. e pathologies were reported in 62 chest CT findings, bilateral in 87% (n � 54) and unilateral in 8% (n � 5) participants. Figure 4 shows the chest CT abnormalities recorded in the patient's files. More than one-third (35%, n � 22) noted ground-glass opacities, whereas 21% (n � 13) had findings suggestive of pneumonia. Patchy lung opacities were seen in 8% (n � 5) of the participants' chest CT scans. Bilateral lung fibrosis and interstitial lung disease were observed in one patient each (1.4%). Chest X-ray scans were done in four (2.5%) participants and were abnormal in three participants, which showed interstitial lung disease with fibrosis, basal pneumonia with fibrosis, and atypical pneumonia, each.

Discussion
In the beginning of the COVID-19 pandemic in Uganda, all patients diagnosed with COVID-19 were hospitalized only in major public health facilities. Private health facilities were only cleared to manage patients with COVID-19 when the number of cases had significantly increased, overwhelming the public health facilities. is is the first study to describe the clinical outcomes of patients with COVID-19 hospitalized in a private facility in Uganda. In this study, we report several important findings. First, over half of the patients in our study presented with severe or critical illness, with about 11% of the patients requiring ICU admission and invasive mechanical ventilation. In the study by Bongomin and colleagues at Mulago National Referral Hospital (MNRH) CTU, a public facility and the largest CTU in Uganda, over 80% of patients presented with severe/critical COVID-19 illness, with up to 20% of patients requiring ICU admissions [17]. e observed difference could be because the majority of patients admitted to MNRH CTU are referral cases from across the country. ese findings agree with the published data showing a high proportion of patients presenting with severe or critical COVID-19 illness during the second wave attributed to the emergence of delta and other variants of the SARS CoV-2 [19,20].
Chest radiographs may be normal in early or mild disease. We noted that about 12% of our participants had normal chest CT images. However, of the 80% of the patients who had abnormal chest imaging findings, over 90% had bilateral disease. Chest imaging is a key in the diagnosis of COVID-19, grading its severity, as well as the investigation of complications such as acute respiratory distress syndrome (ARDS), embolism, and pulmonary infections [21,22]. Although chest CT may be more sensitive than chest radiograph and some chest CT findings may be characteristic of COVID-19, no finding can completely rule in or rule out the possibility of COVID-19. In the United States, the American College of Radiology (ACR) does not recommend using chest CT for screening or diagnosing of COVID-19 and recommends reserving it for hospitalized patients when needed for management. Chest CT in patients with COVID-19 most commonly demonstrates ground-glass opacification with or without consolidative abnormalities, consistent with viral pneumonia [22][23][24].
Secondly, we found an overall in-hospital mortality of approximately 11%, with a significantly higher mortality of 26% during the second wave compared to 5% during the first wave of the COVID-19 pandemic in Uganda. Our findings are consistent with previous reports from Uganda showing a higher mortality during the second wave of the COVID-19 pandemic in Uganda [16,17]. However, the mortality reported in this study is much lower than that reported at MNRH CTU [17]. A higher proportion of patients presenting to MNRH CTU had severe/critical illness compared to those in our setting (>80% versus 52%), and challenges Mortality reported in our study is also much lower than the 32% reported in Cameroon [25], and 48·2% in a cohort study of over 3,000 critically ill patients with COVID-19 pneumonia enrolled in 64 hospitals in ten African countries [26].
In the latter study, in addition to the traditional risk factors for adverse COVID-19 outcome, persons living with HIV/ AIDS and those who experienced delayed access to high-care units and ICU had higher mortality rates. irdly, we showed that advanced age, diabetes mellitus, hypertension, and hypoxemia were significantly associated with mortality. ese findings are consistent with studies from Uganda [17] and several meta-analyses which showed increased severity and mortality in patients with co-morbidities [27,28]. e relationship between COVID-19 and comorbidities such as diabetes mellitus and hypertension are bilateral. With COVID-19 increasing the incidence and exacerbating the control of these conditions, and yet these conditions also worsen COVID-19 outcomes [4,29,30].
ere are currently several drugs recommended by the WHO for the treatment of COVID-19 [31]. ese include the Pfizer combination nirmatrelvir and ritonavir, molnupiravir, sotrovimab, and remdesivir for non-severe disease [31]. Molnupiravir is an oral antiviral agent with clinical utility in the treatment of mild moderate disease, shortening the duration of hospitalization, and halting disease progression to severe or critical illness [31]. Corticosteroids like dexamethasone, tocilizumab (IL-6 receptor blocker), and baricitinib (JAK 1 and JAK 2 inhibitor) are indicated in the management of patients with severe to critical COVID-19 [31]. In this study, we found that remdesivir and ivermectin were each associated with an 80% reduction in mortality. Previous studies have shown that remdesivir may be used as an add-on therapy for patients with severe/critical illness [32,33]. However, recent studies have failed to show any benefit of ivermectin for the treatment of both moderate and severe/critical illness [34].
It is also important to note that only a small proportion of patients in our facility received ivermectin and remdesivir, and the wide confidence interval indicates a lack of precision. erefore, these positive findings should be cautiously interpreted. e massive use of azithromycin and vitamins in our study is attributed to guidance from the first edition of Uganda national guidelines for COVID-19 management recommending their use even for mild-moderate disease [35]. e frequent use of ulinastatin in our study could be supported by studies that reported some studies that reported some benefits, especially for COVID-19 patients with sepsis, or moderate-severe disease [36,37]. Our agreement is that clinicians should follow updated guidelines by their respective health authorities/organization while accounting for the evolving data on the safety and efficacy of various therapeutic agents.
Our study has some important limitations. First, it was a retrospective review of medical records and not all relevant data could be obtained for all participants. For example, no data was extracted on COVID-19 vaccination status of the participants. Secondly, this was a single-center study, recruiting mainly participants from higher socioeconomic status around the capital city, and may not be generalized to other private facilities, particularly in upcountry settings. Despite this, we had a robust dataset including clinical, laboratory, and radiological variables, which provides a better understanding of the complete picture of COVID-19 manifestation in Ugandans. Our findings inform clinical

Conclusions
In conclusion, in a private clinical practice where about half of the patients presented with severe or critical COVID-19 illness, about 1 in 10 died, with a significantly higher proportion of patients dying in the second wave compared to the first wave of the COVID-19 pandemic in Uganda. Most deaths, however, occurred after 7 days of hospitalization.
Data Availability e data that support the findings of this study is available on request from the corresponding author and approval from the administration of Case Hospital, Uganda.

Disclosure
Mirriam Apiyo and Ronald Olum are the co-first authors.

Conflicts of Interest
e authors declare no conflicts of interests.